Abstract
Modulation of immunoreactive endothelin-1 (IR-ET-1) production by vasoactive substances was investigated in cultured endothelial cells (EC) derived from capillaries and microvessels of human brain. Peptides, catecholamines, thrombin, protein kinase C-activating phorbol ester, and calcium ionophore enhanced the secretion of IR-ET-1. The known vasoconstrictive peptides, angiotensin II (Ang II) and arginine-vasopressin (AVP) dose-dependently stimulated the endothelial secretion of IR-ET-1. The angiotensin and vasopressin-inducible production of IR-ET-1 was completely inhibited by their respective receptor antagonists [Sar1, Ala8]-angiotensin II and [1–6 (β-mercapto-β,β-cyclopentamethylene propionic acid), 2-O-methyl-tyrosine]. The results indicate that the peptide-stimulated secretion of IR-ET-1 is receptor-mediated in EC which have specific angiotensin II and arginine-vasopressin receptors. These findings represent the first demonstration of IR-ET-1 production by capillary and microvascular endothelium of human brain.
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Yanagisawa, M., Kurihara, H., Kimura, S., Tomobe, Y., Kobayashi, M., Mitsui, Y., Yazaki, Y., Goto, K., and Masaki, T. 1988. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415.
Itoh, Y., Yanagisawa, M., Ohkubo, S., Kimura, C., Kosaka, T., Inoue, A., Ishida, N., Mitsui, Y., Onda, H., Fujino, M., and Masaki, T. 1988. Cloning and sequence analysis of cDNA encoding the precursor of a human endothelium-derived vasoconstrictor peptide, endothelin: identity of human and porcine endothelin. FEBS Lett. 231:440–444.
Yanagisawa, M., Inoue, A., Takura, Y., Mitsui, Y., Kobayashi, M., and Masaki T. 1989. The human preproendothelin-1 gene: possible regulation by endothelial phosphoinositide turnover signaling. J. Cardiovasc. Pharmacol. 13 (Suppl. 5):S13-S17.
Simonson, M. S., and Dunn, M. J. 1989. Cellular signaling by peptides of the endothelin gene family. Lab. Invest. 64:1–4.
Inoue, A., Yanagisawa, M., Kimura, S., Kasuya, Y., Miyauchi, T., Goto, K., and Masaki, T. 1989. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc. Natl. Acad. Sci. USA 86:2863–2867.
Inoue, A., Yanagisawa, M., Takuwa, Y., Mitsui, Y., Kobayashi, M., and Masaki, T. 1989. The human preproendothelin-1 gene. J. Biol. Chem. 264:13954–14959.
Yanagisawa, M., and Masaki, T. 1989. Molcular biology and biochemistry of the endothelins. TIPS 10:374–378.
Emori, T., Hirata, Y., Ohta, K., Shichir, M., and Marumo, F. 1989. Secretory mechanisms of immunoreactive endothelin in cultured bovine endothelial cells. Biochem. Biophys. Res. Commun. 160:93–100.
Le Monnier de Gouville, A-C., Lippton, H. L., Cevero, I., Summer, W. R., and Hyman, A. L. 1989. Endothelin-a new family of endothelium-derived peptides with widespread biological properties. Life Sci. 45:1499–1513.
Clozel, M., and Fischli, W. 1989. Human cultured endothelial cells do secrete endothelin 1. J. Cardiovasc. Pharmacol. 13 (Suppl. 5): S229–S231.
Vane, J., Anggard, E., and Botting, R. M. 1990. Regulatory functions of the vascular endothelium. N. Engl. J. Med. 323:27–36.
Yoshimoto, S., Ishizaki, Y., Kurihara, H., Sasaki, T., Yoshizumi, M., Yanagisawa, M., Yazaki, Y., Masaki, T., Takakura, K., and Murota, S-I. 1990. Cerebral microvessel endothelium is producing endothelin. Brain Res. 508:283–285.
Hirata, Y., Matsunagae, T., Ando, K., Furukawa, T., Tsukagoshi, G., and Marumo, F. 1990. Presence of endothelin-1-like immunoreactivity in human cerebrospinal fluid. Biochem. Biophys. Res. Comm. 166:1274–1278.
Davenport, A. P., Ashby, M. J., Easton, P., Ella, S., Bedford, J., Dickerson, C., Nunez, D. J., Capper, S. J., and Brown, M. J. 1990. A sensitive radioimmunoassay measuring endothelin-like immunoreactivity in human plasma: comparison of levels in patients with essential hypertension and normotensive control subjects. Clin. Sci. 78:262–264.
Gerhart, D. Z., Broderius, M. A., and Drewes, L. R. 1988. Cultured human and canine endothelial cells from brain microvessels. Brain Res. Bull. 21:785–793.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. 1951. Protein measurement with the folin phenol reagent. J. Biol. Chem. 193:266–275.
Resink, T. J., Hahn, A. W. A., Scott-Burden, T., Powell, J., Weber, E., and Bühler, F. R. 1990. Inducible endothelin mRNA expression and peptide secretion in cultured human vascular smooth muscle cells. Biochem. Biophys. Res. Comm. 168:1303–1310.
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Bacic, F., Uematsu, S., McCarron, R.M. et al. Secretion of Immunoreactive endothelin-1 by capillary and microvascular endothelium of human brain. Neurochem Res 17, 699–702 (1992). https://doi.org/10.1007/BF00968008
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DOI: https://doi.org/10.1007/BF00968008